Study Design and participants
We conducted a case-control study on 53 COVID-19 patients with history of cancer and 106 matched non-cancerous COVID-19 patients as controls in a center served as a government designated hospital (Shariati hospital, Tehran, Iran) for adult COVID-19 patients, from February25th, 2020, to April21st, 2020. The control group were matched in terms of age, gender, underlying disease including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN) and hospitalization time. Transplant recipients (kidney, heart, and bone marrow) were excluded from the study due to control this plausible confounder and high rate of mortality in this subgroup of patients.
All demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from the baseline patients’ medical records. Primary cancer characteristics and detailed treatment information were also obtained by review of the patients’ past medical records.
The study was approved by the ethics committee of Tehran University of Medical Sciences. The ethics committee waived the requirement for informed patient consent for this retrospective study subject to the anonymity of patients.
Study definitions
COVID-19 was diagnosed according to the World Health Organization (WHO) guideline [12] and confirmed by SARS-CoV-2 RNA using the real-time reverse transcription-polymerase chain reaction (RT-PCR) assay of nasal and/or pharyngeal specimens alongside of chest CT scans. Two attending radiologists reviewed all the chest images, independently.
Outcome measures
The following variables were collected from patients’ medical records:
- History and physical examination: age (years), gender (male; female), body mass index (BMI) (weight in kilograms divided by the square of the person's height in meters (kg/m2)), body temperature (when taken orally, °C), systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), respiratory rate (RR), pulse rate (PR), arterial O2 saturation (SO2) (based on pulse oximetry analysis; percent), acid base disorders (pH, pCO2 (milli equivalents per liter; mEq/L), HCO3 (mEq/L) (based on venous blood gas analysis);
- Symptoms: chills, sore throat, fatigue, cough, myalgia, anorexia, chest pain, loss of consciousness, and other symptoms;
- Past Medical History: diabetes, hypertension (HTN), ischemic heart disease (IHD), cancer;
- Laboratory Findings:
- complete blood cell count (CBC), c-reactive protein (CRP) (mg/L), creatinine (milligram per deciliter; mg/dL), blood urea nitrogen (BUN) (mg/dL);
- Liver enzymes: aspartate aminotransferase (AST) (units per liter; U/L), alanine aminotransferase (ALT) (U/L), alkaline phosphatase (ALP) (U/L);
- Total & direct bilirubin (mg/dL);
- Coagulation profile: prothrombin time (PT) (seconds), partial thromboplastin time (PTT) (seconds), international normalized ratio (INR);
- Electrolytes panel (sodium (Na) (millimole/Liter; mmol/L), potassium (K) (mmol/L));
- COVID-19 RT-PCR;
The basis of request or recommendation a laboratory test was influenced by patient's medical needs. Any research protocol was not followed for routine ordering of laboratory tests for participants;
- Lung chest computed tomography (CT)-scan: ground-glass opacity, consolidation, bilateral involvement, chest CT scan total score;
To calculate “chest CT-scan total score,” each lung was divided into three zones, (a) upper zone (above the level of carina), (b) middle zone (between the carina and inferior pulmonary vein) and (c) lower zone (below the level of the inferior pulmonary vein). Each zone was evaluated for the percentage of involvement by either of the mentioned parenchymal abnormalities and was assigned a score from 0-4, 0: no involvement, 1: 1%-25% involved, 2: 26%-50% involved, 3: 51%-75% involved, 4: 76%-100% involved. “chest CT-scan total score” was calculated by summing the scores from all six zones yielding a score between 0 and 24.
- The qSOFA score (also known as quickSOFA): using three criteria, assigning one point for low blood pressure (SBP≤100 mmHg), high respiratory rate (≥22 breaths per minute), or altered mentation (Glasgow coma scale<15);
All of hospitalized adult patients with COVID-19 were treated by lopinavir/ritonavir (kaletra regimen). Antibiotics were appropriately prescribed to treat bacterial infections in eligible participants;
An end-point outcome (that was monitored up to April21st, 2020, the final date of follow-up): severe illness requiring admission to an intensive care unit (ICU), the use of invasive mechanical ventilation, days of hospital stay, or in-hospital death.
Statistical analysis
For descriptive analysis to show the baseline demographic information of the participants included in our analyses, categorical variables were described in frequencies (%). Continuous variables were presented as the mean (standard deviation (SD)) or as the median with interquartile range (IQR), as appropriate. The Shapiro-Wilk test was used to test the normality of data distribution. Parametric and nonparametric tests, including t-test and Mann-Whitney test, were used for comparing quantitative variables and Chi-squared test was applied for comparing categorical variables.
We performed propensity score matching (PSM) using a 1:2 ratio to remove the effect of sex, age, diabetes, hypertension, and ischemic heart disease differences between patients with cancer and patients without cancer. We did this to remove the effects of confounders as much and possible and also needing to check less variables in the multivariable models due to low sample size.
We assessed the effects of several variables on the outcomes of death, ICU admission, and intubation using separate multivariable logistic regression models and a multivariable Poisson regression model (for hospital stay) to estimates the relevant adjusted odds ratios and rate ratio. The variables were chosen based on their clinical importance and their obtainability including level of consciousness, o2sat, systolic blood pressure, temperature, respiratory rate, pulse rate, hemoglobin, white blood cells counts, platelet counts and creatinine. Then, every variable with a p-values less than 0.2 in a univariable model entered the multivariable models.
Statistical analyses were performed using Stata (Corp. 2009. Stata Statistical Software: Release 11. College Station, TX: StataCorp LP.) and the R package MatchIt. Statistical significance was considered as a two-side P-value less than 0.05.